What are examples of humoral immunodeficiencies, particularly in patients with recurrent infections?

Humoral Immunodeficiencies: Clinical Examples

Primary Humoral Immunodeficiencies

The most clinically significant humoral immunodeficiencies include X-linked agammaglobulinemia (Bruton agammaglobulinemia), common variable immunodeficiency (CVID), selective IgA deficiency, IgG subclass deficiency, specific antibody deficiency, and transient hypogammaglobulinemia of infancy. 1

Agammaglobulinemia

• X-linked agammaglobulinemia (Bruton agammaglobulinemia) accounts for 85% of agammaglobulinemia cases and is characterized by extremely low numbers or complete absence of B cells 1
• Autosomal forms of agammaglobulinemia also exist but are less common, similarly presenting with absent B cells 1
• These patients experience recurrent bacterial infections of the upper and lower respiratory tract as the principal clinical manifestation 1

Common Variable Immunodeficiency (CVID)

• CVID presents with variable reduction in 2 or more major immunoglobulin classes, impaired specific antibody responses, and occasionally reduced B-cell numbers 1
• This disorder affects 10% of patients with radiographically-confirmed sinusitis refractory to medical and surgical therapy 1
• CVID patients demonstrate lower IgG levels, greater unresponsiveness to most vaccines, lower percentages of memory and isotype switched-memory B cells, and lower CD4 T-cell counts compared to simple IgG deficiency 2
• 36% of CVID patients present with sinusitis, and these patients have significantly higher prevalence of bronchiectasis and noninfectious complications including autoimmune diseases, lymphoproliferative disorders, and malignancy 1, 2

Selective IgA Deficiency

• Selective IgA deficiency is associated with variably low levels of IgA in serum, sometimes accompanied by impaired specific antibody formation 1
• This represents 6% of patients with radiographically-confirmed sinusitis refractory to medical and surgical therapy 1
• Some patients with selective IgA deficiency may have few or no infections 3

IgG Subclass Deficiency

• IgG subclass deficiency presents with low levels of specific IgG subclasses in serum 1
• The clinical significance of IgG subclass deficiency in patients with recurrent infections remains controversial, and IgG subclasses should not be checked routinely in immunodeficiency evaluation 1

Specific Antibody Deficiency

• Specific antibody deficiency features normal IgG levels but defective response to polysaccharide vaccines 1
• This disorder affects 11% of patients failing medical therapy and undergoing sinus surgery 1

Transient Hypogammaglobulinemia of Infancy

• Transient hypogammaglobulinemia of infancy presents with variably low immunoglobulin levels that resolve with time 1

Clinical Presentation Pattern

• Recurrent bacterial infections of the sinuses, ears, and lungs are the hallmark of antibody deficiency disorders 4
• Infections typically involve encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae 4
• The majority of immunodeficient patients with recurrent sinusitis have defects in humoral immunity 1, 4
• Chronic sinusitis, otitis media, and pneumonia respond poorly to standard antibiotic therapy in these patients 4

Treatment Approach

• For agammaglobulinemia or CVID, therapy consists of antibiotic prophylaxis, IgG replacement, or both 1
• Milder antibody deficiencies (selective IgA deficiency, IgG subclass deficiency, specific antibody deficiency) are most often managed with antibiotic prophylaxis alone 1
• IgG therapy can be applied in selected cases of milder antibody deficiencies 1
• Prophylactic antibiotics remain essential for CVID patients even with adequate IgG replacement to prevent breakthrough infections and manage sinusitis 5

Secondary Humoral Immunodeficiencies

• HIV infection represents a common cause of secondary humoral immunodeficiency, affecting 30% to 68% of patients with chronic or recurrent acute rhinosinusitis 1, 4
• Immunosuppressive medications (corticosteroids, azathioprine) increase infection risk in secondary immunodeficiency 4
• Malnutrition, protein-losing disorders, and hematologic malignancies contribute to secondary immunodeficiency 4
• Iatrogenic causes include surgery (especially splenectomy), radiotherapy, chemotherapy, and immunosuppressive treatments in transplant recipients 6
• B-cell neoplasias (multiple myeloma, chronic lymphocytic leukemia) and renal diseases (nephrotic syndrome, renal insufficiency) induce defective antibody production 6